Multiphase amination process of nitrophenols

ABSTRACT

A PROCESS FOR AMINATING NITROPHENOLS BY REACTION WITH AMMONIA IN A MULTIPHASE LIQUID SYSTEM HAVING AN AQUEOUS PHASE AND AN ORGANIC PHASE. THE PROCESS IS USED TO MAKE NITROANILINE COMPOUNDS IN HIGH YIELD.

A ril 25, 1972 J. CRYER ETAL 3,658,906

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RES/DUE mvsmoas. JOHN c2 Yea meow M, FosTe/a BY THOMAS c. 2555 will 6510mm MM April 25, 1972 J. CRYER ETAL 3,658,906

MULTIPHASE AMINATION PROCESS OF NITROPHENOLS Filed Jan. 21, 1970 2 Sheets-$heet I IOO Fig. 2

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REACT/ON TIME (m INVENTORS. JOHN --c2-rcz HAROLD M. FOSTER BY THO/ 705 C. E555 ATTORNEY United States Patent U.S. Cl. 260-581 11 Claims ABSTRACT OF THEDISCLOSURE A process for aminating nitrophenols by reaction with ammonia in a multiphase liquid system having an aqueous phase and an organic phase. The process is used to make nitroaniline compounds in high yield.

BACKGROUND OF THE INVENTION This invention relates to an improved ammonolysis process for making dinitroanilines from dinitrophenols. In particular it relates to synthesis methods for substituting the hydroxyl group of a dinitrophenol having at least one ortho-nitro group with an amino group. The reaction can be represented as follows:

H (i) NHz OzN OzN Y A Y A B A B I l Z Z where either Y or Z is nitro and the other is selected from the group of hydrogen, alkyl, aryl and halogen; and where A and B are selected independently from hydrogen and lower alkyl.

In general, the ammonolysis reaction can be effected by heating the nitrophenol precursor to a temperature of at least about 120 C. -In the prior art, similar reactions have taken place without a catalyst at higher temperatures. In U.S. Pat. No. 3,111,403, a 2,6-dinitro-4-t-butylphenol is reacted with 27% aqueous ammonium hydroxide at about 175 C. for hours with ether extraction of the black solid residue to recover the corresponding dinitroaniline. These reaction conditions give a low yield as compared to catalyzed reactions.

It is known to use sodium formate as a catalyst in the synthesis of mono-nitroanilines. In U.S. Pat. 2,128,700, 2-nitro-4-methylphenol is reacted with excess ammonia in an aqueous medium with sodium 'formate as' catalyst to give a yield of about 35%. In U.S. Pat. 2,894,988, ammonium chloride is used as a catalyst for the ammonolysis of 2-nitro-4-methylphenol (2-nitro-pcresol) to give yields of more than 90%. However, when the ammonolysis conditions of the prior art teachings are applied to the amination of dinitrophenols having at least one o-nitro group, relatively low yields are obtained.

The dinitroanilines may be used as intermediates in the manufacture of dyes and herbicides. Also, most of the dinitroanilines of the structure defined have herbicidal activity. V

SUMMARY OF THE INVENTION It has been discovered that dinitrophenols can beaminated in high yield using a multi-phase reaction system where one liquid phase comprises water as the reaction phase solvent and a second liquid phase comprises an organic liquid non-miscible with the aqueous reaction phase. High conversion of the precursor nitrophenol with essentially total selectivity to the corresponding nitroaniline can be achieved in a multi-phase system in which an aqueous mixture of ammonia, a nitrogenous salt of a strong acid, and the nitrophenol precursor are charged to a pressure vessel with a hydrophobic organic solvent which has a high solubility for the amination product and is essentially non-miscible with the aqueous solvent of the reaction phase. The ammonolysis reaction can be effected in the temperature range of about C. to 200 C., with high yields being obtained in 3-4 hours at a temperature of to 170 C.

-The ammonolysis reaction mixture is removed from the reaction vessel and the phases separated into an organic liquid phase usually containing a major portion of the amination product, an aqueous phase containing most of the unreacted ammonia, salt and precursor, and a solid phase containing some amination product. These phases are then treated to recover the product and unreacted materials. Overall dinitroaniline yields of about 91 to 93% have been achieved using the process.

THE DRAWING FIG. 1 is a process flow sheet of the process;

FIG. 2 is a semi-logarithmic plot showing the effect of catalyst on product yield;

FIG. 3 is a semi-logarithmic plot of product yield vs. ammonia: phenol ratio; and

FIG. 4 is a reaction rate curve at four difierent temperatures.

DESCRIPTION OF PREFERRED EMBODIMENTS The reaction of a dinitrophenol (DNP') with ammonia to produce dinitroaniline (DNA) product can be carried out in a suitable reaction vessel such as an autoclave equipped with an agitator; The temperature of the reaction can vary from about 100 to 200 C. The preferred temperature range is about 130 to 170 C., with optimum yields being obtained at a temperature of about to C. This reaction usually requires a pressure vessel of inert material capable of withstanding about 20 to 40 atmospheres pressure. Stainless steel (type 316) is a suitable material for constructing the reaction vessel. The reaction time usually runs from about to 24 hours, with optimum yields being obtained at about 3-4 hours. A large excess of ammonia and nitrogenous salt are necessary for high yields.

The process flow sheet for a typical amination reaction and recovery system is shown in FIG. 1. The reactants and solvents are charged to an autoclave 10, reacted under the conditions described herein, and re-' moved from the autoclave to a separator 12. The hydrophobic organic liquid phase, the aqueous liquid phase and the solids are separated mechanically. This may be by decanting, centrifuging, filtering or combination of these. The organic liquid phase usually contains most of the productDNA, which can be recovered by removing the organic solvent, as with a rotary evaporator 14.

The solids from the reactor are extracted with a suitable solvent for the product, such as hot chloroform (CHCI It is understood that other extracting solvents such as toluene or other can be used, but chloroform is used to illustrate the recovery methods. After separating the extracted solids with a filter 16, the chloroform solu tion is washed with water and aqueous ammonia in an extractor 18. The chloroform phase is then evaporated to remove the solvent in rotary evaporator 20 and recover the DNA product.

The undissolved solids from filter 16 are slurried with concentrated hydrochloric acid and separated with a filter 22. Another solvent extraction of the solids from filter 22 with chloroform removes the remaining DNP which is recovered by separating the solid residue with filter 24 and vaporizing the chloroform on rotary evaporator 26. The DNP may be recycled.

The aqueous phase from separator 12 is extracted with chloroform and the phases separated. The chloroform layer is evaporated to give additional DNA product and chloroform is recovered. The aqueous phase from this separation is combined with the aqueous solutions from extractor 18 and filter 22. This combined aqueous mixture is acidified to a pH of about 1 or less, with concentrated hydrochloric acid and filtered to remove watersoluble material. The filter cake is extracted with chloroform which may be combined with a chloroform extraction of the aqueous solution and evaporated to recover DNP. 1

The reaction phase consists essentially of water, ammonia, the DNP precursor and the catalytic salt. The ratio of the reaction phase to the hydrophobic organic liquid phase is not critical if there is sutncient liquid in each phase to permit adequate interfacial contact area for transfer of the amination product from the reaction phase to the second liquid phase and sufiicient organic solvent in the second phase to dissolve the DNA product.

A wide variety of organic liquids have properties suitable for use as the second hydrophobic phase. In general, these liquids should be non-viscous, inert to the reaction conditions and materials, non-miscible with the aqueous reaction phase, and have relatively high solubility for the amination product under reaction conditions. Low solubility for the nitrophenol precursor is also desirable. These requirements are met by numerous organic compounds, including aliphatic hydrocarbons of 5 to 10 carbon atoms, mononuclear aromatic hydrocarbons, cycloaliphatic hydrocarbons, halogenated hydrocarbons, ethers and substituted benzenoids compounds. Examples of operable hydrophobic solvents for use with aqueous media are n-heptane, benzene, toluene, o-dichlorobenzene, diphenyl ether, cyclohexane and nitrobenzene. Toluene is the preferred organic solvent. It is relatively non-toxic, has low flammability and has a very high solubility for the typical amination products of this invention under the reaction conditions. At its normal boiling point 100 parts toluene can dissolve 56 parts of 2,6-dinitro4- methylaniline.

Although some amination occurs with lower amounts of ammonia, the amount of free ammonia present to obtain optimum yields in ammonolysis reaction should be at least 5-10 mols per mol. of DNP. It is preferred to run the reaction with a very large excess of free ammonia, with optimum yields coming from those reaction mixtures containing a molar ratio in the range of about 50:1 to 100:1. This relationship is shown in FIG. 2, where the yield of DNA aniline product is plotted linearly on the ordinate axis and the molar ratio of NH :DNP. precursor is logarithmically plotted on the abscissa. The data shown are from reactions similar to Example I except as noted.

. The concentration of free ammonia in the reaction phase is also important. This is reflected in the H O:NH ratio. Using 29% aqueous ammonia, the 11 mm, molar ratio is about 2.311. When this ratio falls substantially precursor is logarithmically plotted on the abscissa. The appears to be due largely to the loss of selectivity. It has been observed that the molar ratio of H O:N'H can run substantially above 5 :1 without loss of selectivity.

A large amount of a salt of a strong mineral acid with a nitrogenous base is necessary to obtain optimum yield of the dinitroaniline product. The nitrogeneous base may be ammonia or amine and the strong acid may be hydrochloric, hydrobromic, or sulfuric. Mixtures of these bases and acids may be used. The preferred salts are the ammo- 4 nium halides and ammonium chloride is used as the standard catalyst in most of the examples given.

The ratio of ammonium salt to the nitrophenol (DNP) in the reaction mixture has a significant effect upon the percentage theoretical yield. In FIG. 3 a semi-log plot of product yield (wt. percent) vs. molar ratio (NILClzDNP) is shown. This plot isrelated to a series of experiments in which the amount of ammonium chloride is decreased. The standardconditions of Example I are used other than the amount of ammonium salt. -In order to obtain acceptable yields, a molar ratio of ammonium salt to nitrophenol of at least 10:1 should be used with optimum yields being achieved at about 60: 1.

FIG. 4 is a rectilinear plot of reaction time (hours) vs. product yield (rwt. percent) with temperature as the parameter. At 130 C. about 15 hours is required to obtain 80% yield, while the same yields are obtained in [egg than 7 hours at 145 C. and less than 2 hours at 1 C.

The following examples are given to demonstrate the invention; but, the inventive concept is not limited to the specific examples set forth. Unless otherwise stated, all parts are given by weight in the examples.

EXAMPLE I Into a Parr autoclave is charged 10 parts by Weight of 2,6-dinitro-4-methylphenol, 165 parts of ammonium chloride, 270 parts of 29% aqueous ammonia solution, and 173 parts of toluene. The reaction mixture is stirred and heated to 160 C., which developed a pressure of about 25 atmospheres. The reaction is continued for three hours, after which the mixture is cooled, removed from the reaction vessel and separated into an aqueous liquid phase, an organic liquid phase and a solid phase. After filtering the toluene is removed from the organic phase by evaporation to give 2,6-dinitro-4-methylaniline (2,6- dinitro-p-toluidine). The solids can be extracted with toluene or chloroform to recover additional amine. Also, the filtered solids can be recycled with the aqueous phase. Also present in the solid and aqueous phases is the unreacted ammonium salt of 2,6-dinitro-4-methylphenol, which can be recovered by acidification. Using these 4 reaction conditions and recovery methods, an overall process can realize about 9l93% conversion of the phenol, with essentially selectivity of the nitrophenol to the desired amine product.

EXAMPLE II .The procedure of Example I is followed except that the reaction is run at C. for 15 hours. The conversion is 81% at 99% selectivity.

EXAMPLE HI EXAMPLE IV The procedure of Example I is followed except that no toluene lS present and the reaction is run at 130 C. for 5 hours. The conversion is 52% and the selectivity is EXAMPLE V The procedure of Example I is followed except that no ammonium chloride and no toluene are present and I the reaction is run at 130 C. for 5 hours. The conversion is 25% and the selectivity to the desired amine is 56%.

EXAMPLE VI EXAMPLE vn The procedure of Example I is followed except that the nitrophenol is 2,6-dinitro-4-chlorophenol. The conparts) is used as a catalyst and the reaction time is 4.7 hours. The conversion is 21% and the'selectivity to the nitroaniline is 100%.

EXAMPLE XX version is 96% and the selectivity to- 2,6-dinitro-4-chlor0- 5 aniline is 82%.

, EXAMPLE VIII The procedure of Example III 1s repeated except that v p v v 5.8 parts of ammonium sulfite is used as a Bucherer- Example I is followed except that the nitrophenol is type catalyst The conversion is 61% with 8% t y- 2,4-dinitrophenol and the reaction time is 1 hour. The I conversion is 85% and the selectivity .to 2,4-dinitro- 10 EXAMPLE XXI alnlme ls EXAMPLE IX i To demonstrate various methods for introducing the ammonia, the procedure of Example I is repeated except that no ammonia solution is added 260 parts of toluene The procedure of Example I is followed except that are added, 220 parts of Water are added, and the pretenses; tiara:2x3223221 ;a 5:: g g g ee y monium sa 0 mltromet y p eno e converflm selectlvlty to 24'dm1tr'6'sec'butylamlme sion is 83%, with 12% selectivity to the corresponding EXAMPLE X amine. The procedure of Example I is repeated except that 7 EXAMPLE XXII the nitrophenol is 2,4-dinitro-6-methylphenol, the reac- V tion time is 1 hour, and the organic solvent consists of 175 h procedye of Example I 15 followed except t parts f behzerm The phases are separated The Solid 20 parts of dtmtromethylphenol, 54 parts of 29% aquephase is extracted with chloroform to remove 1.7 parts 1 m Parts of toluene Parts of f a 90% 4,6 dinitro o to1uidin mixture with 9.5% montum chloride are reacted at 130 =C. for 5 hours. The 1101 precursor. The extracted solids are treated with conconverslon 1S 19% and the Selectively 1S centrated HCl, filtered, and then extracted with chloroform-to yield 1 part of another mixture of 25.9% di- EXAMPLE XXIII V nitrotoluidine and 72.3% percursor. The remaining solids a 30 The procedure of Example I 18 followed except that g gzgg 1 3 2223132: g i ggg gfg g wlth the catalytic salt is 210 parts of triethylamine hydrochloy ride. Theamine salt is made by mixing triethylamine with EXAMPLE XI I a stoichiometric equivalent of concentrated equeous HCl The procedure of Example X is followed except mat solution andevaporatmg as much water as possible. The the reaction time is 3 hours. The conversion is 100%, 3 9 Wlth 75% selectively to the but only with 58% selectivity to the dinitrotoluidine. dlmtm'4'methylamhne EXAMPLE XII EXAMPLE XXIV The procedure of Example I is repeated except that XXH I the organic solventconsists Of 205 parts by weight of 40 g f procegure 9 i i Th 15 i i gfg n-heptane and the reaction time is two hours. The coni g g gg gg 3 pi gzgz 1S 0 ve-Fswn 1s and the selecuvlty IS 100% In general, the 2,4-dinitrophen0ls are observed to re- EXAMPLE XIII act faster than the 2,6-dinitrophenols. The presence of The procedure of Example I is repeated except that bfanchmg an f P 3 can p some stem: the solvent consists of 260 parts of o-dinchlorobenzenc shown 111 the lsobutyl dImQ'OPhOIIOI and the reaction m is 2 hours e yield is 61%. ample. It IS preferred that the alkyl substituent for Y I and Z in the structural formula be either a lower .EXAMPLES XIV-XVIII branched or unbranched alkyl or higher n-alkyl. Best The elfect of catalyst anion upon the reaction is deresults were obtained with lower alkyls of 1 to 4 carbon monstrated by substituting various ammonium compounds atoms. The aryl substituent 1S preferably mononuclear, for the ammonium chloride. The standard conditions of with good results belng achieved where Z is phenyl. The Example I are used except where noted. The following halogen substttuent preferably has an atomic number of table shows the amounts of each salt used, reaction tem- 9 to 17. A and B may be elther hydrogen or lower alkyl, perature, time, conversion'of DNP, "selectivity of DNA, the same or diiferent. Alkyls having 1 to 4 carbon atoms and wt. percent yield of DNA. appear to have little affect on the ammonolysis reaction TABLE E m ts T T Weight percent tf salts omum lg wt. 6. (1 1 12?) Conversion Selectivity Yield Ch1oride 165 160 2 84 84 at 2 as 250 160 2 37 200 160 2 86 162 160 3.3 88-91 97-100 85-91 1 Large amounts of tar present. Conversion undetermined.

EXAMPLE XIX The procedure of Example III is repeated except that when substituted in the 3 and 5 positions of the phenol ring.

While no particular theory of the ammonolysis reaction is adopted as a necessary part of this disclosure, a

an equivalent amount of ammonium iodide salt (10.3 75 brief discussion of the theoretical aspects of this process may be helpful in understanding the invention. The data support a mechanism such as: 7 i

In theaqueous reaction phase an equilibrium exists between the ionized phenol. Theuseof a large excess of ammonia and a strongly-ionizing ammonium salt forces the reaction to the right with an increase in the amount ofv unionizgied phenol, which ,is believed to; be the reactive species .d uring vammonolysis; If thematic. (K

at}. which decomposition products are being, formed is, nearly equal to the rate (K at, which the ammonblysis reaction proceeds, a steady state will be reached in which" the concentration of DNA .product will remain fairlyconstant while the DNP precursor is converted. By removing the DNA product from the aqueousreaction phase into the hydrophobic organic solvent-phase, the relative reaction rates of K and K can be greatly affected. This results is increased selectivity to t.he. .de-

where either Y or Z is nitro and the other hydrogen,''alkyl of" 1' to halogen; and r r where A and'B are selected independently 'fromhydrogen and lower alkyl, 5 withammonia in a"multiphase reaction system consisting essentially of an aqueous reaction phase containing ammonia, the nitrophenol and a nitrogenous salt of a strong mineral acid and a hydrophobic organic phase is; selected from 4 carbon atoms, phenyl :and:

r 8 which comprises an inert liquid'which has a relatively high solubility-.jonthe --amination product, said. organic liquid being non-miscible with water. 4 2. T he process of claim l-wherein the hydrophobic, or, ganic liquid consists essentially of an aliphatic hydro.- carbon of 5 to 10 carbon atoms, a mononuclear aromatic hydrocarbon, a cycloaliphatic hydrocarbon, a halogenated' hydrocarb on,- an ether or :a 1 substituted benzenoid compound; and wherein the -zaminationprocess has: areaction..temperature-ofabout ::to 200*? (3.; and a reaction time of about /2 to 24 hours. 1

3. The process of claim 2- wherein the salt in the reaction phase contains an ammonium salt of a strong mineral-acid. 1 v

.4. The process of-claim 1=wherein the ,molar ratio of salt of nitrophenol-is at least 5:1.

5.;"The processtoi claim 1 wherein-the molar ratio of water to free ammonia in .the reaction phase is greater than about 2:1. The. process of- -claim 'lwvhereinY isnitrog-Z is selected fromalkyl of 1' to-4 carbon atoms, phenyl' and chlorine i-andrAand Bare; hydrogen. v

-7;--Thelprocess-of claim 6' wherein the-amination proc-: esssrhas. areactiontemperature of'about: :1C. to 170 (3.," and a'reactiontime oflaboutit'fto 4 hours.

8: The process of: claim :7 wherein .the salt in the reaction'ph'ase consists essentially. of an-ammonium salt of a'i'strong mineral "acid and wherein'the molarratio of ammonium: salt to hitrophenol is-at' least about'5 :11.

:9. The process ofclairn-Swherein the'molar'ratio of free ammonia to nitrophehol is at. least 50:1.

10. In the process for converting 2,6-dinitro-4-methylphenol to 2,6-dinitro-4-methylaniline by ammonlysis, the improvement which comprises reacting said phenol with'ammonia"under agitation for about 3 to 4hours at a temperature of about C110 C. in a closed rrionia; 'at'leas't Sfrriols'of ammoniasalt per 'mol of'phenolf and" a 'sufiici'entf amount of hydrophobic organic liquid to dissolve the aniline prodhchsaid organic liquidbeing inert to the reaction conditions,non-miscible with the aqueous reaction phase. 7 v

[11. The? ammonolysis' process ofclaim' 10 wherein the reaction'system'comprises'about 10 parts by weight of the phenol, abou't'270 parts "of 29% aqueousarnmonium' i lielierencescited is 1 UNITED STATES; PATENT S.

JOSEPH REBOLD, Primary Examiner D. M. PAPUGA, Assistant Examiner qg g g UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No '3 5 9 Dated April 5: 97

John Cryer, Harold M. Foster and Thomas C. Rees Inventor(s) It is certified that error. appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below':

a- Column 3, line 66, delete "precursor is logarithmically plotted on the abscissa." and insert therefor below about 2:1, the yields are observed to decrease.

Column 3, line 66, change "The" to This Column 6, line 33, Example XXIII, "equeous" should be aqueous Signed and sealed this 25th day of July 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOfI'TSCHALK Attesting Officer Commissioner of Patents 

